Journal article

Ghrelin-AMPK Signaling Mediates the Neuroprotective Effects of Calorie Restriction in Parkinson's Disease

Jacqueline A Bayliss, Moyra B Lemus, Romana Stark, Vanessa V Santos, Aiysha Thompson, Daniel J Rees, Sandra Galic, John D Elsworth, Bruce E Kemp, Jeffrey S Davies, Zane B Andrews

JOURNAL OF NEUROSCIENCE | SOC NEUROSCIENCE | Published : 2016

Abstract

Calorie restriction (CR) is neuroprotective in Parkinson's disease (PD) although the mechanisms are unknown. In this study we hypothesized that elevated ghrelin, a gut hormone with neuroprotective properties, during CR prevents neurodegeneration in an 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD. CR attenuated the MPTP-induced loss of substantia nigra (SN) dopamine neurons and striatal dopamine turnover in ghrelin WT but not KO mice, demonstrating that ghrelin mediates CR's neuroprotective effect. CR elevated phosphorylated AMPK and ACC levels in the striatum of WT but not KO mice suggesting that AMPK is a target for ghrelin-induced neuroprotection. Indeed, exogenous ghrel..

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Grants

Awarded by Australian National Health and Medical Research Council


Awarded by Australian Research Council


Awarded by NIH


Awarded by Parkinson's UK


Funding Acknowledgements

This work was supported by grants and fellowships from the Australian National Health and Medical Research Council to Z.B.A. (546131, 1084344) and B.E.K.; the Australian Research Council to Z.B.A. (FT100100966); and NIH NS056181 to J.H; and supported in part by the Victorian Government's Operational Infrastructure Support Program (B.E.K.), a St David's Medical Foundation Seed-Corn Grant (J.S.D.) and a Monash University Fellowship to Z.B.A.